This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer's disease is a uniquely human disorder of old age that slowly destroys brain function. Recent research has shown that the disease is associated with a buildup of specific proteins in the brain;one of these proteins is amyloid-[unreadable] (A[unreadable]), a fragment of the amyloid-precursor protein (APP) that forms senile plaques, and the other is the protein tau, which accumulates excessively in nerve cells. Transgenic mouse models have been created to study these proteins, but no mouse model fully resembles human Alzheimer's disease. For example, A[unreadable]-immunization therapy is remarkably successful in reducing A[unreadable] and improving behavior in mice, but in humans with Alzheimer's disease, the same treatment resulted in brain inflammation and shrinkage that were not evident in mouse models. These serious side-effects have impeded the application of this promising treatment to humans. We have generated two transgenic AD monkeys and are currently performing longitudinal studies including cognitive behavioral testing, MRI, routine blood collection for metabolite, genome and proteome profiling study. In addition to AD monkey with the mutant APP gene, we are developing a double transgenic monkey with the mutant APP and human Tau gene in order to enhance AD phenotype.